Download 15Schizophrenia

Schizophrenia
PSY4080 6.0D
Schizophrenia
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Case Study 1
 Mike is a 33 year old divorced white male with
two children he rarely ever sees. He has a college
education and has a degree in computer science.
 Mike says he knows someone has removed his
brain and replaced it with someone else's. He
believes that this brain is controlling him and that
he is not responsible for his actions.
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Case Study 1
 He works everyday and has been on his current
job for 15 years. He says he has lots of friends
but sometimes he thinks its one of them who did
this to him. His family physician has tried to get
him to see a local psychiatrist but Mike refuses to
go.
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Case Study 2
 Jack, 24, graduated from high school and got a job
working in a video store. After working for about 6
months Jack began to hear voices that told him he was
no good. He also began to believe that his boss was
planting small videocameras in the returned tapes to
catch him making mistakes. Jack became increasingly
agitated at work, particularly during busy times, and
began talking strangely to customers.
 For example one customer asked for a tape to be
reserved and Jack indicated that that tape may not be
available because it had “surveilance photos of him that
were being reviewed by the CIA".
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Case Study 2
 After about a year Jack quit his job one night, yelling at
his boss that he couldn't take the constant abuse of
being watched by all the TV screens in the store and
even in his own home.Jack lived with his parents at the
time. He became increasingly confused and agitated. His
parent took him to the hospital where he was admitted.
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Prevalence, Etiology
 1% of population for past 30 years (Thaker &
Carpenter, 2001)
1. Some suggestion that the cause may be genetic
(Miyamoto et al., 2003)
 Heritability (twin studies) up to 90%
 Number of genes have been implicated:
 Dysbindin (DTNBP1): synaptic plasticity, signal
transduction
 Neuregulin (NRG1): neuronal migration and brain
development
 Series of genes related to myelination and/or
oligodendrocyte function
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Prevalence, Etiology
2. Number of environmental factors
 City dwellers (high population density)
 Born during late winter or early spring (Feb to
May)
 (Higher) latitude
 Maternal factors: especially inflammatory
responses to infection, prenatal malnutrition,
stress
 Neonatal factors: Rh incompatibility, prematurity,
low birthweight, complications during delivery
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Symptoms
 Positive (presence is diagnostic)
1. Hallucinations: perceptions of stimuli that are
not actually present
2. Thought disorders: disorganized, irrational
thinking, poor logic, nonsense speech
3. Delusions: beliefs that are contrary to fact
 persecution
 grandeur
 control
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Symptoms
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1.
2.
3.
4.
5.
Negative (absence of normal behaviours)
Flattened emotional response
Poverty of speech
Lack of initiative and persistence
Anhedonia (inability to experience pleasure)
Social withdrawal
 These are not specific to schizophrenia
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Symptoms

Common cognitive impairments: attention, memory and executive
functions (IQ subtests).
•
Often dramatic (two standard deviations below that of healthy controls)
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Growing evidence that cognitive impairments are a distinct
dimension of illness (Keefe and Hawkins, 2006)

May be apparent prior to disease onset, especially areas of
executive functioning.

Sensory and motor performance deficits as well (“neurological soft
signs”)
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DSM-IV Criteria
A. Characteristic symptoms: Two or more of the following,
each present for a significant portion of time during a 1month period (or less if successfully treated):
1) delusions
2) hallucinations
3) disorganized speech
4) grossly disorganized or catatonic behaviour
5) negative symptoms
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DSM-IV Criteria
B. Social/occupational dysfunction: One or more major
areas of functioning such as work, interpersonal relations,
or self-care are markedly below the level achieved prior to
the onset
C. Duration: Continuous signs of the disturbance persist for
at least 6 months.
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DSM-IV Criteria
D. Must exclude Schizoaffective or Mood Disorders
E. Must exclude substance use or general medical
conditions.
F. If there is a history of Pervasive Developmental
Disorders (PDDs), the additional diagnosis of
Schizophrenia is made only if prominent
delusions or hallucinations are also present for
at least 1 month.
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DSM-IV Criteria
Subtypes vary with primary symptoms:
1. Paranoid (delusions or auditory hallucinations)
2. Disorganized (speech or behaviour, flat affect)
3. Catatonic (motoric immobility/stupor or
excessive/excitive motor activity)
4. Undifferentiated
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DSM-IV Criteria
 Associated diagnoses:
1. Schizophreniform disorder (less severe in terms
of symptoms and functioning)
2. Schizoaffective (mood disorder plus delusions or
hallucinations)
3. Delusional disorder (delusions alone:
erotomanic, grandiose, jealous, persecutory,
somatic)
4. Brief psychotic disorder
5. Shared psychotic disorder (folie a deux)
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Neuropathology
1. Dopamine Hypothesis
 Schizophrenia is caused by overactivity of
dopaminergic synapses
 Mesolimbic pathway: ventral tegmental area,
nucleus accumbens, amygdala
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Neuropathology
 Increased dopamine release (Laruelle, et al.,
1996; Brieier et al., 1997)
• D2 receptor hyperexcitability
• DA agonists induce psychotic symptoms in healthy
subjects (cocaine, amphetamine)
• Increased postsynaptic response to dopamine release
(Kestler, Walker, & Vega, 2001)
 Presynaptic DA abnormality
• Dysfunction in storage and metabolism at the axon
terminal (hyper-responsiveness)
 Prolonged activation of postsynaptic receptors
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Neuropathology
2. The Serotonergic Hypothesis
 Serotonergic hyper-excitability can also produce
hallucinations (I.e. LSD)
 5-HT 2A and 1A receptor subtypes appear to be the one of
the sites of action of atypical antipsychotics
 Serotonergic pathways in pre-frontal cortex may be disrupted
or impaired in schizophrenics
There is likely a disruption of all monoamine pathways
in the mesolimbic/mesocortical pathway
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Neuropathology
3. Brain Abnormalities shown postmortem, or with
CT, PET, MRI
 Not related to loss of tissue, rather to disrupted
developmental processes (neuron size, increased
cellular packing density)
 Reduction (bilateral) in the size of the
hippocampus
 Enlargement of the ventricles (non-specific to
schizophrenia)
 Reduced brain volume overall
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Neuropathology
4. A neurodevelopmental disorder?
 Abnormalities of early brain development
increase risk for subsequent clinical symptoms
 Established correlation between developmental
pathology (precursory/prodromal symptoms) and
adult psychosis
 Schizophrenia may degenerative, with worsening
of function over time
 Association between first-episode psychosis and
structural brain changes
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Neuropathology
4. A neurodevelopmental disorder?
 Seems to be associated with some physical
dysmorphisms (Schiffman et al., 2002)
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head circumference too large or small
two or more hair whorls (cowlicks)
wide-set eyes
low-set or asymmetrical ears
high palate
curved fifth finger, single crease in palm
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Neuropathology
 Recent research suggests that some neural
degeneration may occur in adolescents with
early-onset schizophrenia
 Thompson et al (2001) - loss of cortical gray
matter volumne starting in parietal lobes and
progressing through temporal and frontal lobes
• May be related to prenatal influences being activated by
pubertal hormones, or stresses associated with
adolescence.
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Neuropathology
4. Different symptoms caused by separate
pathways.
 Positive symptoms are caused by hyperactivity
of DA synapses in nucleus accumbens (Carr &
Sesack, 2000).
 Negative symptoms are caused by brain
abnormalities, particularly loss of frontal neurons
• Hypo-excitability of (dorsolateral) prefrontal cortex
• Reduction of inhibition
• Associated with less activation of the frontal lobes on
PET (Taylor, 1996)
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